Conway E L, Louis W J, Jarrott B
Eur J Pharmacol. 1978 Dec 1;52(3-4):271-80. doi: 10.1016/0014-2999(78)90279-0.
Acute administration of alpha-methyldopa (200 mg kg-1 s.c.) produced a short-lived decrease in dopamine levels in 5 regions of the rat brain. Maximal dopamine depletion was 55% in the corpus striatum and over 75% in other regions and occurred 4--6 h after alpha-methyldopa injection; dopamine levels recovered within 12 h. Maximal noradrenaline depletion of over 80% occurred in all regions 4--24 h after alpha-methyldopa and after 24 h noradrenaline levels were still significantly reduced from control values. In these acute studies alpha-methyldopamine accumulated rapidly in amounts equal to or greater than the depleted dopamine in all regions, reaching a peak at 4 h. By contrast, alpha-methylnoradrenaline accumulated more slowly reaching a peak at 6--24 h and was never present in amounts greater than the depleted noradrenaline. Following chronic administration of alpha-methyldopa (40 mg kg-1 s.c., twice daily 5 days) there was a similar depletion of noradrenaline and dopamine to that seen in the acute studies. The depletion was associated with a much smaller accumulation of alpha-methyldopamine. The striking feature of these results, however, was the large accumulation of alpha-methylnoradrenaline in all brain regions. This probably reflects the slow turnover and resistance to degradation by monoamine oxidase of alpha-methylnoradrenaline.
皮下注射α-甲基多巴（200毫克/千克）可使大鼠脑内5个区域的多巴胺水平出现短暂下降。纹状体内多巴胺的最大耗竭量为55%，其他区域超过75%，在注射α-甲基多巴后4 - 6小时出现；多巴胺水平在12小时内恢复。在α-甲基多巴注射后4 - 24小时，所有区域的去甲肾上腺素最大耗竭量超过80%，24小时后去甲肾上腺素水平仍显著低于对照值。在这些急性研究中，α-甲基多巴胺在所有区域迅速积累，其量等于或大于耗竭的多巴胺，在4小时达到峰值。相比之下，α-甲基去甲肾上腺素积累较慢，在6 - 24小时达到峰值，其含量从未超过耗竭的去甲肾上腺素。长期皮下注射α-甲基多巴（40毫克/千克，每日两次，共5天）后，去甲肾上腺素和多巴胺的耗竭情况与急性研究相似。这种耗竭与α-甲基多巴胺的积累量小得多有关。然而，这些结果的显著特点是所有脑区中α-甲基去甲肾上腺素大量积累。这可能反映了α-甲基去甲肾上腺素的周转缓慢以及对单胺氧化酶降解的抗性。
